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Techniques and interpretation of measurement of the CD4 cell count in HIV-infected patients

Paul E Sax, MD
John G Bartlett, MD
Section Editor
Martin S Hirsch, MD
Deputy Editor
Jennifer Mitty, MD, MPH


CD4 T-cell laboratory testing through flow cytometry is considered an essential part of HIV care, since this parameter is used to stage disease and guide clinical management. Certain CD4 T cell thresholds are used as benchmarks to either initiate prophylaxis against opportunistic infections (OIs) and/or to begin antiretroviral therapy (ART). The CD4 cell count is also a relatively consistent indicator of treatment response [1]. Thus, it is important for clinicians to learn about the techniques and interpretation of flow cytometry and to understand the factors that may lead to variations in test results.

This topic will address flow cytometry and other techniques for measuring CD4 T cells and the various factors that can affect CD4 cell counts, such as medications, infections, and other conditions. Issues related to the immunology and pathogenesis of HIV infection and the use of HIV RNA testing are discussed elsewhere. Guidance on when to start ART or OI prophylaxis is discussed elsewhere. (See "Techniques and interpretation of HIV-1 RNA quantitation" and "Selecting antiretroviral regimens for the treatment-naïve HIV-infected patient" and "Overview of prevention of opportunistic infections in HIV-infected patients".)


CD4 and CD8 T cells — Human T lymphocytes can be functionally divided into cells that provide help for other immune cells and those that mediate cellular cytotoxicity. Helper T lymphocytes express cluster determinant 4 (abbreviated as "CD4") whereas cytotoxic T cells express cluster determinant 8 (abbreviated as "CD8"). The CD4 and CD8 molecules are members of the immunoglobulin superfamily and mediate adhesion to major histocompatibility complex class II and class I molecules, respectively. In addition, CD4 and CD8 amplify stimulatory signals through the T cell receptor [2-4].

A CD4:CD8 ratio is calculated by dividing the number of CD4+ T cells by the number of CD8+ T cells; this ratio is usually greater than 1 in immunocompetent individuals [5]. However, in HIV infection, the CD4:CD8 ratio is usually less than 1. This reflects increasing numbers of CD8+ T cells and depletion of CD4+ T cells in chronic infection. This ratio usually increases with the initiation of antiretroviral therapy (ART) although the CD4:CD8 ratio normalizes in only a minority of patients [6].

How does HIV affect CD4 T cells? — HIV infection leads to severe depletion of CD4 T cells in the gut-associated lymphoid tissue with subsequent reduced levels of circulating CD4 lymphocytes in the peripheral blood [7]. CD4 cells are reduced precipitously in acute HIV infection, but usually rebound in the blood over several weeks as HIV-specific CD8 T cells help to lower plasma viremia [8]. In the untreated patient, CD4 T cells subsequently decline over several years. Population-based studies of the natural history of HIV infection among men who have sex with men (MSM) show that the mean CD4 count prior to seroconversion is about 1000 cells/microL; CD4 counts decline to a mean of 780 cells/microL at six months post-seroconversion and to 670 cells/microL at one year of follow-up [9]. Subsequently, the CD4 cell count declines at an average yearly rate of approximately 50 cells/microL, but there is substantial variation among patients [9-11]. Significant depletion of CD4 T cells can lead to opportunistic infections and mortality in the untreated patient. The stages and natural history of HIV infection are discussed elsewhere. (See "The natural history and clinical features of HIV infection in adults and adolescents".)

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Literature review current through: Nov 2017. | This topic last updated: Apr 20, 2017.
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